Association between use of proton pump inhibitors and non-typhoidal salmonellosis identified following investigation into an outbreak of Salmonella Mikawasima in the UK, 2013.

In November 2013, national public health agencies in England and Scotland identified an increase in laboratory-confirmed Salmonella Mikawasima. The role of proton pump inhibitors (PPIs) as a risk factor for salmonellosis is unclear; we therefore captured information on PPI usage as part of our outbreak investigation. We conducted a case-control study, comparing each case with two controls. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression. Thirty-nine of 61 eligible cases were included in the study. The median age of cases was 45 years; 56% were female. Of these, 33% were admitted to hospital and 31% reported taking PPIs. We identified an association between PPIs and non-typhoidal salmonellosis (aOR 8·8, 95% CI 2·0-38·3). There is increasing evidence supporting the existence of an association between salmonellosis and PPIs; however, biological studies are needed to understand the effect of PPIs in the pathogenesis of Salmonella. We recommend future outbreak studies investigate PPI usage to strengthen evidence on the relevance of PPIs in Salmonella infection. These findings should be used to support the development of guidelines for patients and prescribers on the risk of gastrointestinal infection and PPI usage.

A foodborne outbreak of Salmonella Bareilly in the United Kingdom, 2010.

We report the preliminary findings of the investigation of an outbreak of foodborne Salmonella Bareilly. Between August and November 2010, there were 231 laboratory-confirmed reports of S. Bareilly in the United Kingdom. A case­control study showed that consumption of bean sprouts was significantly associated with illness. The investigation concluded that raising public awareness to ensure the correct preparation of raw bean sprouts during cooking was the principal means of preventing further cases.

Are UK graduates equipped with the skill set required to meet the demands of the UK's edentulous population?

As the UK witnesses a decline in the number of edentulous adults, there is a simultaneous reduction in the number of cases available to undergraduate dental students for the teaching of complete dentures. When edentulous adults are unable to function with conventional complete dentures, particularly pertaining to the mandibular denture, an implant-supported mandibular overdenture has been evidenced as the gold standard for edentulous patients. The evidence in favour of mandibular implant-supported overdentures is one of the most robust evidence bases for any clinical treatment and similarly it has been shown that undergraduate students are equally as capable in the provision of implant-supported overdentures as experienced prosthodontists. Yet there appears to be a disparity in the General Dental Council's undergraduate learning outcomes pertaining to care for edentulous adults. Furthermore, the UK seems to be falling behind in this respect in comparison to our European, American and Australian colleagues. This review looks at the evidence for the provision of implant-supported overdentures in the setting of the undergraduate dental curriculum, the potential barriers within this teaching forum and how well prepared UK undergraduates are for the clinical management of edentulous patients in the future.

Trends in mortality following Clostridium difficile infection in Scotland, 2010-2016: a retrospective cohort and case-control study.

BACKGROUND: National surveillance of Clostridium difficile infection (CDI) in Scotland enables the monitoring of trends in incidence rates but not mortality. AIM: To assess factors associated with mortality for all CDI cases aged ≥15 years in Scotland between 2010 and 2016. METHODS: All CDI cases aged ≥15 years in Scotland between 2010 and 2016 were linked to hospital admission and mortality datasets. Logistic regression was used to assess factors associated with mortality (30-day all-cause). A case-control study of a hospitalized subset of cases and matched hospitalized controls assessed the impact of CDI on mortality and length of stay. FINDINGS: Thirty-day all-cause mortality decreased over the seven-year period (from 20.5% to 15.6%; P < 0.001), mainly among healthcare-associated CDI (HA-CDI). Increased age, higher Charlson score, HA-CDI, as well as liver, heart and malignancy comorbidities were associated with higher mortality. No association was observed between polymerase chain reaction ribotype and higher mortality, though 015 and 078 were associated with lower mortality. Adjusted odds ratio (OR) for 30-day mortality in hospitalized CDI cases compared to controls was 2.67 (95% confidence interval (CI): 2.42-2.94; P < 0.001). Whereas mortality declined over time in cases and controls, the trend in ORs remained relatively stable. Having CDI increased additional mean length of stay beyond infection by 22.3% (95% CI: 18.0-26.8%; P < 0.001). CONCLUSION: CDI is associated with an almost three-fold increase in 30-day mortality and places an increased burden on hospital resources by increasing mean LOS beyond the infection date by 22.3%. The decreasing CDI mortality trends may be due to overall improvements in mortality among the general and hospital population of Scotland. Therefore, despite large declines in incidence rates, CDI remains a serious healthcare problem.

Isolation of different serovars of Salmonella enterica from wild birds in Great Britain between 1995 and 2003.

Postmortem examinations were carried out on the carcases of 779 wild birds. Salmonellosis was a common cause of death in greenfinches (Carduelis chloris), house sparrows (Passer domesticus) and chaffinches (Fringilla coelebs), and was also responsible for the deaths of other birds such as goldfinches (Carduelis carduelis), feral pigeons and different species of gulls. Most cases of salmonellosis in finches occurred between January and March, whereas salmonellosis in house sparrows tended to occur between October and March. Salmonella Typhimurium DT40 and DT56 (variant) predominated in finches and sparrows, DT41 and DT195 were the most common strains isolated from gulls, and DT2 and DT99 were recovered from feral pigeons. These "wild bird" strains of Salmonella made up less than 0.5 per cent of the isolates of Salmonella recovered from cattle, sheep, pigs, chickens or turkeys in Great Britain over the same period, but they made up nearly 3 per cent of the isolates from more extensively reared avian livestock such as gamebirds, ducks and geese.

EPCR Ser219Gly: elevated sEPCR, prothrombin F1+2, risk for coronary heart disease, and increased sEPCR shedding in vitro.

We have progressively analysed three studies of coronary heart disease (CHD) for a variant in EPCR (Ser219Gly). Initially, in a prospective study, NPHSII, while no overall CHD-risk was identified in heterozygotes, homozygotes for 219Gly exhibited a three-fold elevated risk (HR 3.3, CI 1.22-8.96). In diabetics within NPHSII, there was a suggestion that 219Gly+ was associated with elevated CHD-risk (HR 1.89, CI 0.39-9.06) although numbers were small. To further assess the effect of the variant in diabetes, a case-control study of MI, HIFMECH, was used, in which previous analysis had defined a group with metabolic syndrome, by factor analysis. A significant CHD-risk interaction was identified between genotype and the 'metabolic syndrome' factor (interaction p=0.009). To further assess CHD-risk for this variant in type-2 diabetes and to assess the effect of the variant upon thrombin generation and plasma levels of soluble EPCR, a cross-sectional study of type-2 diabetes was used. A significant CHD-risk was identified for European Whites (OR 2.84, CI 1.38-5.85) and Indian Asians in this study (OR 1.6, CI 1.00-2.57) and the frequency of 219Gly was two-fold higher in Indian Asians. Soluble EPCR levels were strongly associated with genotype, with homozygotes for 219Gly having four-fold higher levels (p<0.0001). In vitro studies of EPCR-transfected cells suggested increased basal release of sEPCR from cells expressing the 219Gly EPCR phenotype. Furthermore, in base-line samples from NPHSII and in the diabetic study, a significant increase in prothrombin F1+2 level was observed for 219Gly. The increased CHD-risk and thrombin generation appears to be acting through increased shedding of the Gly allele from the cell surface.

Further monitoring for Salmonella species and Escherichia coli O86 at a bird table in south-west Scotland.

Pooled faeces collected from a garden bird table were screened for Salmonella species and Escherichia coli O86, two recognised causes of garden bird mortality. Dead birds found at the site were also screened for these organisms, and bird numbers and meteorological data were recorded. In the first year of the study, 48.5 per cent of the samples were positive for Salmonella Typhimurium DT56 (variant), decreasing to 38.9 per cent in the second year and 12.8 per cent in the third year. E. coli O86 was not recovered from any of the 288 samples of pooled faeces tested. S. Typhimurium DT56 (variant) was recovered from the carcases of eight birds found dead at the site, and E. coli O86 was isolated from three carcases. The degree of contamination of the bird table with S. Typhimurium DT56 (variant) was positively correlated with the number of house sparrows observed in the garden, but not with the number of blackbirds, chaffinches or greenfinches.

Cardiovascular outcomes in type 2 diabetes. A double-blind placebo-controlled study of bezafibrate: the St. Mary's, Ealing, Northwick Park Diabetes Cardiovascular Disease Prevention (SENDCAP) Study.

OBJECTIVE: To determine whether serum lipid intervention, in addition to conventional diabetes treatment, could alter cardiovascular outcomes in type 2 diabetes. RESEARCH DESIGN AND METHODS: There were 164 type 2 diabetic subjects (117 men, 47 women) without a history of clinical cardiovascular disease randomized to receive either bezafibrate or placebo daily on a double-blind basis in addition to routine diabetes treatment and followed prospectively for a minimum of 3 years. Serial biochemical and noninvasive vascular assessments, carotid and femoral artery B-mode ultrasound measurements, and those pertaining to coronary heart disease (CHD)--clinical history, the World Health Organization (WHO) cardiovascular questionnaire, and resting and exercise electrocardiogram (ECG)--were recorded. RESULTS: Bezafibrate treatment was associated with significantly greater reductions over 3 years in median serum triglyceride (-32 vs. 4%, P = 0.001), total cholesterol (-7 vs. -0.3%, P = 0.004), and total-to-HDL cholesterol ratio (-12 vs. -0.0%, P = 0.001), and an increase in HDL cholesterol (6 vs. -2%, P = 0.02) as compared with placebo. There was a trend toward a greater reduction of fibrinogen (-18 vs. -6%, P = 0.08) at 3 years. No significant differences between the two groups were found in the progress of ultrasonically measured arterial disease. In those treated with bezafibrate, there was a significant reduction (P = 0.01, log-rank test) in the combined incidence of Minnesota-coded probable ischemic change on the resting ECG and of documented myocardial infarction. CONCLUSIONS: Improving dyslipidemia in type 2 diabetic subjects had no effect on the progress of ultrasonically measured arterial disease, although the lower rate of "definite CHD events" in the treated group suggests that this might result in a reduction in the incidence of coronary heart disease.

Implications of new diagnostic criteria for abnormal glucose homeostasis in women with previous gestational diabetes.

OBJECTIVE: To determine the consequences of applying revised American Diabetes Association (ADA) (1997) and World Health Organization (WHO) (1998) recommendations for the classification of glucose intolerance in women with previous gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: There were 192 women with previous GDM who took an oral glucose tolerance test (OGTT) 1-86 months after delivery and were classified by WHO (1985), ADA (1997, fasting glucose), and revised WHO (1998) guidelines. RESULTS: Among the 165 women without a preexisting diagnosis of diabetes, WHO-1985 and ADA-1997 provided similar estimates of diabetes prevalence (13.3% vs. 11.5%) but widely differing estimates of impaired glucose homeostasis (31.5% impaired glucose tolerance [IGT] by WHO-1985 vs. 10.9% impaired fasting glucose by ADA-1997 criteria). Overall, 56 women (34%) showed a classification discrepancy between WHO-1985 and ADA-1997 criteria, including 44 with normal fasting glucose by ADA-1997 criteria, but abnormal 2-h glucose by WHO-1985 criteria (40 IGT, 4 diabetes). The cardiovascular risk profile of these women was more favorable than that of 18 women with impaired fasting glucose. WHO-1998 recommendations reproduced ADA-1997 findings when used as a fasting screen, but behaved similarly to WHO-1985 criteria when 2-h glucose values were also analyzed. CONCLUSIONS: All criteria produced similar estimates of diabetes prevalence. However, analyses based on a single fasting glucose screen (and a threshold of 6.1 mmol/l) failed to identify 60% of women with abnormal 2-h glucose levels. Screening women with previous GDM (and by analogy, other groups at high risk of diabetes) with a single fasting glucose has low sensitivity for the detection of abnormal glucose tolerance. Recent guidelines recommending this approach require reevaluation.

Vasopressin in human cerebrospinal fluid.

Arginine vasopressin was measured by RIA in samples of plasma and cerebrospinal fluid (CSF) taken synchronously from 62 patients with proven or suspected disorders of the central nervous system in order to determine the relationship between the secretion of vasopressin into the systemic circulation and that into the CSF. In 12 patients without endocrine or brain disease, mean plasma values (+/- SD) were 2.8 +/- 0.7 pg/ml and CSF values were 2.4 +/- 0.7 pg/ml. Thirty-six patients with various intracranial disorders had plasma and CSF values which were both within the range of 1-4 pg/ml. Eight patients had raised plasma concentrations, but their CSF levels were within the normal range. One patient with posttraumatic diabetes insipidus and 2 patients with subarachnoid hemorrhage had concentrations of CSF vasopressin which were greater than plasma levels. These results indicate that a blood CSF barrier to vasopressin exists in man and that under certain pathological conditions excessive amounts of the hormone can be secreted into the CSF independently of that which is released into the blood, a finding which could have clinical significance in disorders of brain function.

Retinal blood flow changes during pregnancy in women with diabetes.

PURPOSE: To study retinal blood flow (RBF) during pregnancy in subjects with and without diabetes and to relate the changes to progression in diabetic retinopathy. METHODS: RBF in a major temporal retinal vein was measured, where possible, during all three trimesters (T1 to T3) and the postpartum period (PP) using laser Doppler velocimetry (measuring velocity [V]) and monochromatic fundus photographs (measuring diameter [D]). RESULTS: In the subjects without diabetes (n = 19), no significant change in RBF was demonstrated. V was significantly greater in T3 than in PP (P = 0.01). D was significantly smaller in T1 to T3 than in PP (P < or = 0.01). RBF in the subjects with diabetes was significantly higher in T2 and T3 than in PP (P < 0.05). V increased from T1 to T2 (P = 0.04) and decreased from T2 to PP (P = 0.001) and from T3 to PP (P = 0.002). The only significant change in D was a smaller value in T1 than in PP (P = 0.003). However, it was only those subjects whose DR progressed (n = 11) who had a significant increase in RBF during pregnancy (P = 0.0001). CONCLUSIONS: These data suggest that the hyperdynamic circulation present in pregnancy led to compensatory retinal vessel constriction (autoregulation) in the group without diabetes; this was largely absent in the patients with diabetes, with resultant increase in retinal blood flow associated with worsening retinopathy. This finding lends further support to the hypothesis that increased retinal blood flow is a pathogenic mechanism for diabetic retinopathy.

An attempt to identify the evolutionary origin of a novel serotype of Salmonella enterica isolated from harbour porpoises.

The isolation since 1991 of a new serotype of Salmonella enterica (antigenic formula 4,12:a:-) from harbour porpoises (Phocoena phocoena) at post-mortem examination raised the question of its evolutionary origin. Representative strains of S. enterica serotype 4,12:a:- and strains of eight other serotypes of serogroup 04 with phase-1 flagellar antigen H 'a' were examined by EcoRI ribotyping, IS200 fingerprinting and PCR-based profiling. Statistical analysis of results of multiple typing showed that strains of Salmonella serotype 4,12:a:- were genetically distant from those of antigenically similar salmonella serotypes, none of which seemed likely to be the progenitor of the 'porpoise' serotype.

Leucocyte and erythrocyte magnesium levels after jejuno-ileal bypass surgery.

Leucocyte magnesium concentration was measured in 25 hypomagnesaemic patients following a jejuno-ilean bypass operation for gross obesity. The mean plasma magnesium concentration in the bypass group was 0.67 mmol/l compared with that of 0.90 mmol/l in a group of 17 healthy volunteers, but the leucocyte magnesium concentration in the two groups was not significantly different. The plasma potassium was found to be significantly lower in the bypass group but there was no significant difference in the leucocyte potassium concentration in the two groups. Simultaneous measurements of erythrocyte magnesium, sodium and potassium were made. There was no evidence of intracellular magnesium depletion on the basis of the tissues studied.

Hypomagnesaemia in diabetes.

The plasma magnesium (Mg) concentrations of 582 unselected diabetic outpatients and 140 control subjects were measured by atomic absorption spectrophotometry. Mean plasma Mg (+/-S.D.) was significantly lower in the diabetic patients (0.737 +/- 0.071 mmol/l) than in the control subjects (0.810 +/- 0.057 mmol/l), and 146 (25%) diabetics had values below those of all control subjects except one. Plasma Mg correlated best with clinic blood glucose concentration (r = -0.32, p less than 0.001) and other significant associations were observed with glycosuria, age, sex, insulin therapy and biguanide therapy. Although its significance is unclear, hypomagnesaemia could conceivably predispose to ischaemic heart disease in diabetes.

Evaluation of a non-mydriatic camera in Indian and European diabetic patients.

The value of the Canon CR3-45NM non-mydriatic fundus camera in screening for diabetic retinopathy has been assessed in two ethnic groups, namely, 45 Indian and 40 European diabetic patients. There was 72% agreement between ophthalmoscopy by an ophthalmologist and the photographic assessment, and 100% agreement on clinically important lesions requiring treatment. However, peripheral retinal lesions, seen on ophthalmoscopy but lying outside the photographic field, occurred in 4% of eyes. 6% of photographs were totally unassessable and an additional 12% were only partially assessable. The prevalence and severity of retinopathy was similar in Indian and European patients. The advantages and disadvantages of the non-mydriatic camera in screening for diabetic retinopathy are discussed.

The Eluru survey: prevalence of known diabetes in a rural Indian population.

Asian Indian migrants have a strikingly high diabetes prevalence but prevalence in India has been considered to be relatively low. However, there have been few recent studies, especially in rural India. A house-to-house survey was undertaken in a defined area of Eluru, a small town in South India, and in four adjoining villages. A total of 9563 subjects (4729 male, 4834 female) were surveyed, of whom 5699 lived in Eluru and 3864 in the four villages. Enquiry was made for known diabetes in each household. In all, 157 known diabetic subjects (89 male, 68 female) were ascertained. The prevalence of known diabetes was 6.1% in all subjects aged 40 or over and rose to 13.3% in the age group 50-59 years. The overall crude prevalence of known diabetes was 1.6% (1.9% male, 1.4% female). The prevalence in Eluru (1.5%) was similar to that in the four villages (1.9%). The age-adjusted rates for known diabetes in the middle-aged and elderly subjects are unexpectedly high, considering the poor socio-economic circumstances, decreased health awareness and decreased access to medical facilities, and are comparable with those of similar surveys in relatively affluent Delhi, and in Southall, London. The prevalence in rural (as well as urban) India may be much higher than previously realised. Large formal prevalence studies are urgently required.

Helicobacter pylori infection and upper gastrointestinal patholgy in a British immigrant Indian community.

OBJECTIVES: To assess the pattern of upper gastrointestinal pathology and the prevalence of Helicobacter pylori infection in the Southall Indian community. DESIGN: A prospective study of endoscopic findings in 124 Indian and 107 whites from the Southall area. In a separate study blood samples were taken from 100 Indian subjects presenting to a single general practitioner in Southall. METHODS: The presence of gastritis and H. pylori infection was assessed histologically in Indian and white patients undergoing endoscopy. Serum samples were analysed using a specific enzyme-linked immunosorbent assay (ELISA) for anti-H. pylori immunoglobulin G. RESULTS: In the endoscopic study, Indian and white patients had the same rate of H. pylori infection (52% vs. 43%, respectively) (P= NS). The pattern of upper gastrointestinal pathology was similar in whites and Indians. In the general practice based study 41 subjects were H. pylori seropositive. Seropositivity increased with age (P<0.05). CONCLUSION: There is no excess of H. pylori-related pathology in Southall immigrant Indians. The similarity of upper gastrointestinal pathology in UK Indian and white patients presenting for endoscopy suggests that the high rates of duodenal ulceration, gastritis and H. pylori infection in India are environmentally rather than racially determined.

Investigation of human infections with Salmonella enterica serovar Java in Scotland and possible association with imported poultry.

PFGE analysis of S. Java strains (29 from humans, 30 from poultry meat) showed two major clusters. All isolates from poultry imported from the Netherlands belonged to Cluster A, which also comprised 10 human isolates. Thirty-one of the 37 isolates in this cluster had an identical JavX1 pattern, similar to the X8 profile of a particular S. Java clone predominant in poultry production in several European countries. Cluster B comprised 19 human isolates and two poultry isolates of unknown origin. These results combined with epidemiological data and information on the origins of poultry meat strongly suggested that imported poultry meat is an important source of Java infections in humans in Scotland.

Atherosclerosis risk factors: variation in healthy hospital workers and members of local communities asymptomatic for vascular disease. Implications for normal controls.

The major risk factors for atherosclerosis were measured in 100 middle-aged members of the local community aged between 40 and 66 attending hospital for minor operations, hernia repair, varicose veins or endoscopy, and their healthy accompanying spouses. Levels in this group were compared with those measured in 75 age- and sex-matched hospital workers. Ten of the 12 risk factors measured were more unfavourable in the local population (P = 0.039). Levels of total cholesterol (P = 0.0013), low-density lipoprotein (LDL) cholesterol (P = 0.0002) and body mass index (P = 0.0074) were higher in members of the local community. There was no difference in levels of triglycerides, high-density lipoprotein cholesterol, von Willebrand factor (vWf, an index of damage to the endothelial cell), fibrinogen, glucose, systolic and diastolic blood pressure, waist-to-hip ratio or the proportion of smokers. We also found systolic blood pressure (P = 0.014) and vWf (P = 0.021) to be higher, while high-density lipoprotein (P = 0.022) was lower in the 35 smokers, but we could not identify any factor that correlated with age. However, systolic (P = 0.028) and diastolic (P = 0.0072) blood pressures, triglycerides (P = 0.029) and waist-to-hip ratio (P < 0.0001) were all lower, while high-density lipoprotein was higher (P < 0.0001) in the 80 women compared to the men. We conclude that precise definition of the identity of the control group is necessary in studies of risk factors for atherosclerosis, or in frank disease, if mis-interpretation is to be avoided.

Twice-daily insulin regimens in management of severe diabetes.

Diurnal glucose profiles have been compared in ten insulin dependent diabetics receiving, firstly, a twice-daily soluble insulin (SI): isophane insulin (NPHI) insulin (30% SI, 70% NPHI). For each patient the two regimens gave similar profiles though nocturnal blood glucose control was better on Mixtard. HbA1 values were similar on the two regimens. The findings show that, using highly purified formulations, small changes in insulin proportions in twice-daily SI: NPHI regimens may be irrelevant to diabetic control; they also suggest that highly purified NPHI may have a substantially shorter duration of action than its older counterpart and that the convenient regimen of twice-daily Mixtard is usually as good as any more complicated 'tailormade' regimen of highly purified insulins.